This invention relates to methods and compositions for rapid and enduring improvement in blood flow to the heart and for the prompt relief of inadequate myocardial function.
This invention is a continuation of U.S. Ser. No. 08/680,684, filed Jul. 17, 1996.
Angina pectoris, the syndrome of chest pain or tightness commonly elicited by exertion or emotional stress, and occasionally appearing in the absence of provocation (as unstable angina), is caused by inadequate blood flow through the coronary arteries. The subsequent deprivation of oxygen (ischemia) to the myocardium triggers pain and discomfort by an unknown mechanism. Appearance of angina in an otherwise well patient is of medical concern because it indicates the presence of an obstructive lesion or partial stenosis of one or more coronary arteries, usually as the result of the buildup of atherosclerotic plaque. Angina is often taken to be an indication for the initiation of one form or another of invasive cardiac revascularization, such as percutaneous transluminal angioplasty (PCTA), or cardiac artery bypass grafting (CABG). Both therapies carry significant intraprocedural risk and the failure rate, as measured by the need for repetition, can be significant.
One benefit of revascularization is palliation of the symptoms of angina. Of considerable concern to the patient, the onset of chest pain and/or tightness reinforces an awareness of the fragility of their existence. The resulting concern about and avoidance of activities which may provoke further symptoms can lead to a debilitating preoccupation with morbidity and restriction of daily activities. In many cases the principal benefit of invasive revascularization may be relief of the symptoms of angina.
The proximate cause of angina, narrowing of the coronary arteries, is the outcome of a slowly evolving progressive stenosis of the artery lumen by atherosclerotic plaque and spasm of the artery in the vicinity of the plaque. Many factors contribute to the development of plaque and spasm, including high levels of certain plasma lipoproteins, cigarette smoking, hypertension, heritable risk factors, and the contributions of noncardiovascular diseases such as diabetes. An important constituent of plaque is cholesterol, and hypercholesterolemia is an important risk indicator.
Medical treatment of hypercholesterolemia over an extended period of time has been shown to result in objective widening of the lumen of arteries narrowed by atherosclerosis. The benefits of medical treatment are generally not rapid, however, and prompt and enduring improvement in myocardial function, with concurrent rapid symptomatic relief of the pain and discomfort of angina has not been reported in the medical literature.
At present, angina is treated medically by the use of nitrates, principally nitroglycerin and isosorbide dinitrate, which promote vascular perfusion by serving as a reservoir from which the endothelial relaxing factor, nitric oxide, can be formed. Although nitrates provide relief, their short duration of action and relatively constrained ability to prevent new episodes, in certain respects, limit their utility. Moreover, treatment of angina with nitrates does not induce an enduring improvement in cardiovascular status. Also, long term exposure to nitrates may result in thickening of coronary musculature and an increased tendency toward myocardial infarction.
Although the literature contains many references to the use of one or several of the medication components described herein, there has been no description to date of a treatment program which combines aggressive cholesterol lowering with marine lipid loading. This combination is shown here to promote rapid and enduring improvement in myocardial function.